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protein and AKI

Vladimir Maksimov, Eriko Oya, Mayo Tanaka, Takayuki Kawaguchi, Aki Hachisuka, Karl Ekwall, Pernilla Bjerling, Jun-Ichi Nakayama
The binding of heterochromatin protein 1 (HP1) to lysine 9-methylated histone H3 (H3K9me) is an essential step in heterochromatin assembly. Chp2, an HP1-family protein in the fission yeast Schizosaccharomyces pombe, is required for heterochromatic silencing. Chp2 recruits SHREC, a multifunctional protein complex containing the nucleosome remodeler Mit1 and the histone deacetylase Clr3. Although the targeting of SHREC to chromatin is thought to occur via two distinct modules regulated by the SHREC components Chp2 and Clr2, it is not clear how Chp2's chromatin binding regulates SHREC function...
2018: PloS One
Joshua C Bis, Xueqiu Jian, Brian W Kunkle, Yuning Chen, Kara L Hamilton-Nelson, William S Bush, William J Salerno, Daniel Lancour, Yiyi Ma, Alan E Renton, Edoardo Marcora, John J Farrell, Yi Zhao, Liming Qu, Shahzad Ahmad, Najaf Amin, Philippe Amouyel, Gary W Beecham, Jennifer E Below, Dominique Campion, Camille Charbonnier, Jaeyoon Chung, Paul K Crane, Carlos Cruchaga, L Adrienne Cupples, Jean-François Dartigues, Stéphanie Debette, Jean-François Deleuze, Lucinda Fulton, Stacey B Gabriel, Emmanuelle Genin, Richard A Gibbs, Alison Goate, Benjamin Grenier-Boley, Namrata Gupta, Jonathan L Haines, Aki S Havulinna, Seppo Helisalmi, Mikko Hiltunen, Daniel P Howrigan, M Arfan Ikram, Jaakko Kaprio, Jan Konrad, Amanda Kuzma, Eric S Lander, Mark Lathrop, Terho Lehtimäki, Honghuang Lin, Kari Mattila, Richard Mayeux, Donna M Muzny, Waleed Nasser, Benjamin Neale, Kwangsik Nho, Gaël Nicolas, Devanshi Patel, Margaret A Pericak-Vance, Markus Perola, Bruce M Psaty, Olivier Quenez, Farid Rajabli, Richard Redon, Christiane Reitz, Anne M Remes, Veikko Salomaa, Chloe Sarnowski, Helena Schmidt, Michael Schmidt, Reinhold Schmidt, Hilkka Soininen, Timothy A Thornton, Giuseppe Tosto, Christophe Tzourio, Sven J van der Lee, Cornelia M van Duijn, Badri Vardarajan, Weixin Wang, Ellen Wijsman, Richard K Wilson, Daniela Witten, Kim C Worley, Xiaoling Zhang, Celine Bellenguez, Jean-Charles Lambert, Mitja I Kurki, Aarno Palotie, Mark Daly, Eric Boerwinkle, Kathryn L Lunetta, Anita L Destefano, Josée Dupuis, Eden R Martin, Gerard D Schellenberg, Sudha Seshadri, Adam C Naj, Myriam Fornage, Lindsay A Farrer
The Alzheimer's Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants...
August 14, 2018: Molecular Psychiatry
Egor Y Plotnikov, Anna A Brezgunova, Irina B Pevzner, Ljubava D Zorova, Vasily N Manskikh, Vasily A Popkov, Denis N Silachev, Dmitry B Zorov
Neonatal sepsis is one of the major causes of mortality and morbidity in newborns, greatly associated with severe acute kidney injury (AKI) and failure. Handling of newborns with kidney damage can be significantly different compared to adults, and it is necessary to consider the individuality of an organism's response to systemic inflammation. In this study, we used lipopolysaccharide (LPS)-mediated acute kidney injury model to study mechanisms of kidney cells damage in neonatal and adult rats. We found LPS-associated oxidative stress was more severe in adults compared to neonates, as judged by levels of carbonylated proteins and products of lipids peroxidation...
August 8, 2018: Antioxidants (Basel, Switzerland)
Katsuyoshi Ando, Mikihiro Fujiya, Yoshiki Nomura, Yuhei Inaba, Yuuya Sugiyama, Takuya Iwama, Masami Ijiri, Keitaro Takahashi, Kazuyuki Tanaka, Aki Sakatani, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Yusuke Mizukami, Toshikatsu Okumura
Background/Aims: Venous thromboembolism (VTE) is a major extraintestinal manifestation in inflammatory bowel disease (IBD), regarded as an independent risk factor for VTE according to reports from Western countries. However, the incidence and risk factors of VTE in Asian IBD patients are not fully understood. We aimed to reveal the incidence and risk factors of VTE in Japanese IBD inpatients. Methods: The incidence of VTE in inpatients with IBD (n=340), gastrointestinal cancers (n=557), and other gastrointestinal diseases (n=569) treated at our hospital from 2009 to 2013 was retrospectively investigated...
July 2018: Intestinal Research
Hiromasa Tsujiguchi, Daisuke Hori, Yasuhiro Kambayashi, Toshio Hamagishi, Hiroki Asakura, Junko Mitoma, Masami Kitaoka, Enoch Olando Anyenda, Thao Thi Thu Nguyen, Yohei Yamada, Koichiro Hayashi, Tadashi Konoshita, Takiko Sagara, Aki Shibata, Satoshi Sasaki, Hiroyuki Nakamura
BACKGROUND: Sedentary behaviors have recently become an important public health issue. We aimed to investigate the relationship between screen time and nutrient intake in children and adolescents. METHODS: The present study was conducted in 2013. Data were collected from children and adolescents aged between 6 and 15 years old in Shika town. Questionnaires were distributed to 1459 subjects, 1414 of whom participated in the study (96.9%). Sedentary behaviors were assessed based on participants' screen behaviors (television (TV) viewing, personal computer (PC) use, and mobile phone (MP) use)...
August 7, 2018: Environmental Health and Preventive Medicine
Shuang Li, Bingbing Qiu, Hong Lu, Yunshi Lai, Jixing Liu, Jiajun Luo, Fengxin Zhu, Zheng Hu, Miaomiao Zhou, Jianwei Tian, Shouyi Yu, Fan Yi, Jing Nie
AIMS: The risk factors promoting acute kidney injury (AKI) to chronic kidney disease (CKD) progression remains largely unknown. The aim of the present study was to investigate whether hyperhomocysteinemia (Hhcy) accelerates the development of renal fibrosis after AKI. RESULTS: Hhcy aggravated ischemia-reperfusion-induced AKI and the subsequent development of renal fibrotic lesions characterized by excessive extracellular matrix deposition. Mechanistically, the RNA binding protein human antigen R (HuR) bound to the 3'-untranslated region (3'-UTR) of heme oxygenase-1 (HO-1) mRNA...
August 7, 2018: Antioxidants & Redox Signaling
Hideaki Usui, Akiko Nishiwaki, Lanors Landiev, Johannes Kacza, Wolfram Eichler, Rina Wako, Aki Kato, Noriaki Takase, Soichiro Kuwayama, Kazuki Ohashi, Yousef Yafai, Andreas Bringmann, Ayae Kubota, Yuichiro Ogura, Johannes Seeger, Peter Wiedemann, Tsutomu Yasukawa
Age-related macular degeneration (AMD) is a leading cause of legal blindness in people over 50 years of age in many developed countries. Drusen are yellowish extracellular deposits beneath retinal pigment epithelium (RPE) found in aging eyes and considered as a biomarker of AMD. However, the biogenesis of drusen has not been elucidated. We reported previously that multicellular spheroids comprised of human RPE cells constructed a well-differentiated monolayer of RPE with Bruch's membrane. We determined that RPE spheroids exhibited drusen formation between RPE and Bruch's membrane with expression of many drusen-associated proteins such as amyloid ß and complement components, the expression of which was altered by a challenge with oxidative stress...
August 6, 2018: Journal of Cell Science
Lusy Handoko, Bogumil Kaczkowski, Chung-Chau Hon, Marina Lizio, Masatoshi Wakamori, Takayoshi Matsuda, Takuhiro Ito, Prashanti Jeyamohan, Yuko Sato, Kensaku Sakamoto, Shigeyuki Yokoyama, Hiroshi Kimura, Aki Minoda, Takashi Umehara
The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23...
August 6, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Paolo Menè, Elisa Giammarioli, Claudia Fofi, Giusy Antolino, Giacinto La Verde, Agostino Tafuri, Giorgio Punzo, Francescaromana Festuccia
BACKGROUND/AIMS: Multiple myeloma (MM) represents 10% of all haematologic malignancies. Renal involvement occurs in 50% of MM patients; of them, 12-20% have acute kidney injury (AKI), with 10% needing dialysis at presentation. While hemodialysis (HD) has no effect upon circulating and tissue levels of monoclonal proteins, novel apheretic techniques aim at removing the paraproteins responsible for glomerular/tubular deposition disease. High cut-off HD (HCO-HD) combined with chemotherapy affords a sustained reduction of serum free light chains (FLC) levels...
August 3, 2018: Kidney & Blood Pressure Research
Jinhong Li, Ying Tang, Patrick M K Tang, Jun Lv, Xiao-Ru Huang, Christine Carlsson-Skwirut, Lydie Da Costa, Anna Aspesi, Suada Fröhlich, Pawel Szczęśniak, Philipp Lacher, Jörg Klug, Andreas Meinhardt, Günter Fingerle-Rowson, Rujun Gong, Zhihua Zheng, Anping Xu, Hui-Yao Lan
Macrophage migration inhibitory factor (MIF) is elevated in patients with acute kidney injury (AKI) and is suggested as a potential predictor for renal replacement therapy in AKI. In this study, we found that MIF also plays a pathogenic role and is a therapeutic target for AKI. In a cisplatin-induced AKI mouse model, elevated plasma MIF correlated with increased serum creatinine and the severity of renal inflammation and tubular necrosis, whereas deletion of MIF protected the kidney from cisplatin-induced AKI by largely improving renal functional and histological injury, and suppressing renal inflammation including upregulation of cytokines such as interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), IL-6, inducible nitric oxide synthase (iNOS), MCP-1, IL-8, and infiltration of macrophages, neutrophils, and T cells...
July 17, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Dong Sun, Xin Wan, Bin-Bin Pan, Qing Sun, Xiao-Bing Ji, Feng Zhang, Hao Zhang, Chang-Chun Cao
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), which could induce the poor prognosis. The purpose of this study was to characterize the molecular mechanism of the functional changes of CDllb+/Ly6Cintermediate macrophages after renal IRI. The gene expression profiles of CDllb+/Ly6Cintermcdiate macrophages of the sham surgery mice, and the mice 4 h, 24 h and 9 days after renal IRI were downloaded from the Gene Expression Omnibus database. Analysis of mRNA expression profiles was conducted to identify differentially expressed genes (DEGs), biological processes and pathways by the series test of cluster...
February 2018: Current medical science
Jianchun Chen, Huaizhou You, Yan Li, You Xu, Qian He, Raymond C Harris
BACKGROUND: Increasing evidence indicates that renal recovery from AKI stems from dedifferentiation and proliferation of surviving tubule epithelial cells. Both EGF receptor (EGFR) and the Hippo signaling pathway are implicated in cell proliferation and differentiation, and previous studies showed that activation of EGFR in renal proximal tubule epithelial cells (RPTCs) plays a critical role in recovery from ischemia-reperfusion injury (IRI). In this study, we explored RPTC activation of Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ), two key downstream effectors of the Hippo pathway, and their potential involvement in recovery from AKI...
August 2, 2018: Journal of the American Society of Nephrology: JASN
Anna Hall, Siobhan Crichton, Matt Varrier, Danielle E Bear, Marlies Ostermann
BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) has emerged as a new sepsis biomarker. It is not known whether suPAR has a role in critically ill patients with severe acute kidney injury (AKI). METHODS: Our main aims were to describe serial serum suPAR concentrations in patients with severe AKI, to investigate a potential association between suPAR and C-reactive protein (CRP), and to compare suPAR and CRP as diagnostic markers of infection in patients with AKI...
August 2, 2018: BMC Nephrology
Ali C Johnson, Richard A Zager
P21 is up-regulated in renal tubules in response to AKI and localizes in the nucleus where it induces cell cycle arrest (CCA). These events can mitigate early injury, but can also facilitate the onset of the cellular senescence/"aging" process. Hence, we asked: i) Can renal p21 up-regulation be gauged by plasma and/or urinary p21 assay? ii) Might p21 serve as an AKI / CCA biomarker? and iii) Does p21 accumulate during normal renal aging, and might plasma p21 reflect this process? Mice were subjected to either ischemia-reperfusion (I/R) or nephrotoxic (maleate) AKI...
August 1, 2018: American Journal of Physiology. Renal Physiology
Shinya Tashiro, Jose M M Caaveiro, Makoto Nakakido, Aki Tanabe, Satoru Nagatoishi, Yasushi Tamura, Noriyuki Matsuda, Dali Liu, Quyen Q Hoang, Kouhei Tsumoto
DJ-1 is a Parkinson's disease associated protein endowed with enzymatic, redox sensing, regulatory, chaperoning, and neuroprotective activities. Although DJ-1 has been vigorously studied for the last decade and a half, its exact role in the progression of the disease remains uncertain. In addition, little is known about the spatiotemporal regulation of DJ-1, or the biochemical basis explaining its numerous biological functions. Progress has been hampered by the lack of inhibitors with precisely known mechanisms of action...
July 31, 2018: ACS Chemical Biology
Aya Tokinaga-Uchiyama, Taichi Mizushima, Kazunori Akimoto, Yoji Nagashima, Kazunori Sasaki, Masa-Aki Nakaya, Kenichi Ohashi, Kazumi Kubota, Yasuyo Maruyama, Hisamori Kato, Fumiki Hirahara, Etsuko Miyagi, Shigeo Ohno, Mikiko Asai-Sato
We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0% of SCC cases, aPKCλ/ι was expressed more abundantly than in normal epithelium, but there was no significant association between aPKCλ/ι intensity and disease progression (P=0...
July 27, 2018: International Journal of Gynecological Pathology
Xiao-Li Yuan, Chun-Sheng Li, Yun Zhang, Ji-Yang Ling, Qiang Zhang, Yong Liang, Bo Liu, Lian-Xing Zhao
Background: Acute kidney injury (AKI) frequently occurs in cardiopulmonary resuscitation patients. Studies comparing the effects of extracorporeal membrane oxygenation (ECMO) with conventional cardiopulmonary resuscitation (CCPR) on AKI were rare. This study aimed to compare the effects of ECMO with those of CCPR on survival rate and AKI and explore the underlying mechanisms in a swine model of cardiac arrest (CA). Methods: Sixteen male pigs were treated with ventricular fibrillation to establish CA model and then underwent CCPR (CCPR group, n = 8) or ECMO during cardiopulmonary resuscitation (ECPR group, n = 8)...
August 5, 2018: Chinese Medical Journal
Xiuju Sun, Qingxia Luan, Shujuan Qiu
In this study, the protective effect of valsartan against glycerol-induced acute kidney injury (AKI) in male albino rats was investigated. Valsartan is used to treat high blood pressure and congestive heart failure and can prolong lifespan following a heart attack. The rats were divided into control, AKI, AKI + valsartan 100 mg/kg bw, and AKI + valsartan 200 mg/kg bw groups. Superoxide dismutase, glutathione peroxidase, catalase, lipid peroxidation, and reduced glutathione were assessed, and histopathological, immunohistochemical and western blot analyses were performed...
July 25, 2018: International Journal of Biological Macromolecules
Faeq Husain-Syed, Fiorenza Ferrari, Aashish Sharma, Tommaso Hinna Danesi, Pércia Bezerra, Salvador Lopez-Giacoman, Sara Samoni, Massimo de Cal, Valentina Corradi, Grazia Maria Virzì, Silvia De Rosa, María Jimena Muciño Bermejo, Carla Estremadoyro, Gianluca Villa, Jose J Zaragoza, Carlotta Caprara, Alessandra Brocca, Horst-Walter Birk, Hans-Dieter Walmrath, Werner Seeger, Federico Nalesso, Monica Zanella, Alessandra Brendolan, Davide Giavarina, Loris Salvador, Rinaldo Bellomo, Mitchell H Rosner, John A Kellum, Claudio Ronco
Background: Cardiac surgery is a leading cause of acute kidney injury (AKI). Such AKI patients may develop progressive chronic kidney disease (CKD). Others, who appear to have sustained no permanent loss of function (normal serum creatinine), may still lose renal functional reserve (RFR). Methods: We extended the follow-up in the observational 'Preoperative RFR Predicts Risk of AKI after Cardiac Surgery' study from hospital discharge to 3 months after surgery for 86 (78...
July 19, 2018: Nephrology, Dialysis, Transplantation
Tatsuya Mimura, Hideharu Funatsu, Hidetaka Noma, Masahiko Shimura, Yuko Kamei, Maiko Yoshida, Aki Kondo, Emiko Watanabe, Atsushi Mizota
PURPOSE: To compare aqueous humor levels of various cytokines between patients with age-related macular degeneration (AMD) and cataract patients. METHODS: Thirteen eyes with wet-type AMD (AMD group) and 14 eyes with cataract (cataract group) were studied. Aqueous humor levels of 11 factors (vascular endothelial growth factor receptors, growth factors, and inflammatory factors) were measured by the suspension array method. RESULTS: Aqueous humor levels of vascular endothelial growth factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2, and inflammatory factors (monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, and IL-8) were significantly higher in the AMD group than in the cataract group (all p < 0...
July 26, 2018: Ophthalmologica. Journal International D'ophtalmologie
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